PMID- 29510001
OWN - NLM
STAT- MEDLINE
DCOM- 20181026
LR  - 20191210
IS  - 1742-7843 (Electronic)
IS  - 1742-7835 (Linking)
VI  - 123
IP  - 3
DP  - 2018 Sep
TI  - Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, 
      After Intravenous or Subcutaneous Administration in Healthy Subjects.
PG  - 294-300
LID - 10.1111/bcpt.13001 [doi]
AB  - Tildrakizumab, a high-affinity humanized IgG1k antibody that selectively binds 
      interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function, 
      is under investigation for treatment of moderate-to-severe chronic plaque 
      psoriasis. The objective of this analysis was to assess the pharmacokinetics, 
      bioavailability and safety/tolerability of single ascending doses of 
      tildrakizumab after intravenous (IV) and subcutaneous (SC) dosing in healthy 
      subjects. P05661 was a phase 1, single-dose, randomized, placebo-controlled study 
      of tildrakizumab IV doses of 0.1, 0.5, 3 and 10 mg/kg, or placebo. P05776 was a 
      phase 1, single-dose, randomized, placebo-controlled study of tildrakizumab SC 
      doses of 50 or 200 mg, or placebo. After either single IV or SC dosing, 
      tildrakizumab exhibited slow systemic clearance (CL), limited volume of 
      distribution and a long t(1/2) . Both the C(max) and the area under the curve 
      (AUC) increased proportionally with doses from 0.1 to 10 mg/kg, or 50-200 mg. The 
      bioavailability of SC dosing was ~80% (90% CI: 62-103%) for 50 mg and ~73% (90% 
      CI: 46-115%) for 200 mg, respectively, versus 0.5 and 3 mg/kg IV. Across both 
      studies, six of 43 evaluable subjects were positive for post-dose antidrug 
      antibodies; two of these were positive for neutralizing antibodies. Most adverse 
      events (AEs) were mild; the most frequent AEs included upper respiratory tract 
      infection and headache. Single doses of tildrakizumab 0.1, 0.5, 3 and 10 mg/kg 
      administered IV or single doses of 50 and 200 mg administered SC were safe and 
      well tolerated in healthy adult subjects.
CI  - (c) 2018 Nordic Association for the Publication of BCPT (former Nordic 
      Pharmacological Society).
FAU - Khalilieh, Sauzanne
AU  - Khalilieh S
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Hodsman, Peter
AU  - Hodsman P
AD  - Centre for Clinical Studies, Melbourne, Vic., Australia.
FAU - Xu, Christine
AU  - Xu C
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Tzontcheva, Anjela
AU  - Tzontcheva A
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Glasgow, Shirley
AU  - Glasgow S
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Montgomery, Diana
AU  - Montgomery D
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20180420
PL  - England
TA  - Basic Clin Pharmacol Toxicol
JT  - Basic & clinical pharmacology & toxicology
JID - 101208422
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Dermatologic Agents)
RN  - 0 (Interleukin-23)
RN  - DEW6X41BEK (tildrakizumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects/pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Antibodies, Neutralizing/*immunology
MH  - Area Under Curve
MH  - Biological Availability
MH  - Dermatologic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Interleukin-23/*immunology
MH  - Male
MH  - Middle Aged
MH  - Tissue Distribution
MH  - Young Adult
EDAT- 2018/03/07 06:00
MHDA- 2018/10/27 06:00
CRDT- 2018/03/07 06:00
PHST- 2017/12/12 00:00 [received]
PHST- 2018/02/26 00:00 [accepted]
PHST- 2018/03/07 06:00 [pubmed]
PHST- 2018/10/27 06:00 [medline]
PHST- 2018/03/07 06:00 [entrez]
AID - 10.1111/bcpt.13001 [doi]
PST - ppublish
SO  - Basic Clin Pharmacol Toxicol. 2018 Sep;123(3):294-300. doi: 10.1111/bcpt.13001. 
      Epub 2018 Apr 20.